Muscle wasting occurs rapidly in critically ill patients and impacts both short and long term outcomes. Altered protein metabolism drives muscle loss in ICU patients, with muscle protein breakdown exceeding muscle protein synthesis (MPS). Interventions aimed at attenuating muscle loss by stimulating MPS rates are hampered by a lack of knowledge on altered muscle protein turnover rates during critical illness. Only a few studies have specifically assessed muscle protein synthesis by using contemporary intravenous stable isotope infusions, which allows the assessment of MPS over a short (\<9 hours) period of time. Results from such acute studies can be difficult to extend or translate into long-term clinical practice and outcomes. Oral deuterated water (2H2O) dosing provides an alternative method that can be utilized to extend the measurement of muscle protein synthesis over a period of several days or weeks. It could therefore provide a valuable tool to study muscle protein synthesis during ICU admission and the impact of different anabolic interventions. Although multiple studies using the deuterated water methodology have been performed in both healthy volunteers and patients, it has not yet been performed in critically ill patients. In this prospective study the investigators aim to assess fractional rates of muscle protein synthesis over a period of (maximal) 7 days in critically ill patients admitted to the intensive care unit. Secondly, the investigators aim to assess mechanisms of acute muscle wasting on an microscopic, ultrastructural and molecular level. Furthermore, the investigators aim to investigate to what extent muscle fibre size is recovered 3 months after ICU discharge.
Study Type
OBSERVATIONAL
Enrollment
20
Jessa Hospital
Hasselt, Limburg, Belgium
RECRUITINGmuscle protein synthesis rate (%/h)
obtained by using deuterated water, muscle biopsy sampling and blood sampling
Time frame: 7 days of stay at the intensive care unit
skeletal muscle fiber characteristics 1
cross sectional area of muscle fibers
Time frame: 7 days of stay at the intensive care unit
skeletal muscle fiber characteristics 2
amount and distribution of muscle fibers (distribution will be calculated as: amount of type X / total amount of fibres)
Time frame: 7 days of stay at the intensive care unit
mRNA expression in skeletal muscle tissue 1
mRNA expression in skeletal muscle tissue of MAFBx (atrophy marker)
Time frame: 7 days of stay at the intensive care unit
mRNA expression in skeletal muscle tissue 2
mRNA expression in skeletal muscle tissue of MurF1 (atrophy marker)
Time frame: 7 days of stay at the intensive care unit
mRNA expression in skeletal muscle tissue 3
mRNA expression in skeletal muscle tissue of FOXO (atrophy marker)
Time frame: 7 days of stay at the intensive care unit
patient characteristic- age
age in years
Time frame: 7 days of stay at the intensive care unit
patient characteristic- body weight
body weight in kg
Time frame: 7 days of stay at the intensive care unit
patient characteristic- height
height in m
Time frame: 7 days of stay at the intensive care unit
patient characteristic- sex
male or female
Time frame: 7 days of stay at the intensive care unit
patient characteristics (medical1)
mechanical ventilation (duration in days)
Time frame: 7 days of stay at the intensive care unit
patient characteristics (medical2)
comorbidities (list of comorbidities)
Time frame: 7 days of stay at the intensive care unit
patient characteristics (medical3)
reason hospital admission
Time frame: 7 days of stay at the intensive care unit
patient characteristic- APACHE score II
APACHE II score = acute physiology score + age points + chronic health points. Minimum score = 0; maximum score = 71.
Time frame: 7 days of stay at the intensive care unit
patient characteristic- food intake
food intake (energy in kcal and protein intake in g/kg/d)
Time frame: 7 days of stay at the intensive care unit
patient characteristic- LOS
Length of stay ICU and hospital (in days)
Time frame: Stay at the intensive care unit and Hospital (up to 1 year)
muscle volume
3d ultrasound assessed at follow up visit
Time frame: 3 months post-hospital discharge
habitual food
Assessed using questionnaires at follow up visit (higher score means better intake)
Time frame: 3 months post-hospital discharge
habitual activity
Assessed using questionnaires at follow up visit (higher score means better intake)
Time frame: 3 months post-hospital discharge
muscle hand grip strength
hand grip strength using the JAMAR dynamometer in kg
Time frame: 3 months post-hospital discharge
leg muscle strength
1RM upper leg at follow up visit
Time frame: 3 months post-hospital discharge
Functional capacity 1
SPPB at follow up visit (short physical performance battery)
Time frame: 3 months post-hospital discharge
Functional capacity 2
6min walking test at follow up visit
Time frame: 3 months post-hospital discharge
Quality of life questionnaire
SF-36 at follow up visit (Short Form Health Survey 36 items) range score between 0-100, lower score represents great health related problems
Time frame: 3 months post-hospital discharge
Quality of life questionnaires
Euro-QoL-5D-5-level at follow up visit (Euro quality of life 5 Dimension 5 level) Answers can be converted into EQ-5D index, an utility scores anchored at 0 for death and 1 for perfect health
Time frame: 3 months post-hospital discharge
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